The importance of the thymus gland in the development maintenance and aging of the immune system is now generally accepted. The thymus has both an endocrine and cellular component which contribute to initiating and maintaining the ability to combat invasions by pathogens or neoplastic tissue and in preventing autoimmune disease. The impetus for the proposed study is based upon the previous isolation and partial characterization of thymosin in our laboratory and the demonstration that this thymic hormone could partially or fully reconstitute immune functions in thymic deprived animals and most recently in humans with immunodeficiency diseases. The research proposed in this study has the following objectives: (1) to isolate, characterize, and compare each of the active polypeptide components of bovine and human thymosin, fraction 5; (2) to develop new and relevant methods of assaying thymosin's actions; (3) to elucidate the role of the endocrine thymus in immunological function including the ontogenesis and senescence with aging of lymphoid tissues' reactive capability. Experimental approaches to accomplish these objectives include: (1) determination of the amino acid sequence of the active polypeptide components of both bovine and human thymosin; (2) definition of thymosin's role in immunological responses involving blastogenesis, lymphokine release, helper function and suppressor function; (3) evaluation of thymosin treatment on the functional capabilities of lymphocyte populations from normal, aged, thymectomized, or otherwise immunosuppressed mice, and animal models of primary immunodeficiency diseases (nude mice).